Similar Datasets
Project description:Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88-CD1c+CD163+ DCs (called DC3s) as immediate precursors of inflammatory CD88-CD14+CD1c+CD163+FcεRI+ DCs. DC3s develop via a specific pathway activated by GM-CSF, independent of cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. Like classical DCs but unlike monocytes, DC3s drove activation of naive T cells. In vitro, DC3s displayed a distinctive ability to prime CD8+ T cells expressing a tissue homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor β (TGF-β) signaling. In vivo, DC3s infiltrated luminal breast cancer primary tumors, and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity.
| S-EPMC7445430 | biostudies-literature
Project description:Dendritic cells (DC) are antigen presenting cells controlling T cell activation. In human, the diversity, ontogeny and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88-CD1c+CD163+ DC (termed as DC3) as an immediate precursor of inflammatory CD88-CD14+CD1c+CD163+FcεRI+ DC. DC3 develop via a specific pathway activated by GM-CSF, independent from the cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. As classical DC, but unlike monocytes, DC3 drove the activation of naïve T cells. In vitro, DC3 displayed a distinctive ability to prime CD8+ T cells expressing a tissue-homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor-b (TGF-β) signaling. In vivo, DC3 infiltrated luminal breast cancer primary tumors and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Altogether, these findings define DC3 as a lineage of inflammatory DC endowed with a strong potential to regulate tumor immunity.
2020-05-23 | GSE151072 | GEO
Project description:Transcriptional and functional analysis of CD1c+ human dendritic cells identifies a CD163+ subset priming CD8+CD103+ T cells
| PRJNA634664 | ENA
Project description:Transcriptional and functional analysis of CD1c+ human dendritic cells identifies a CD163+ subset priming CD8+CD103+ T cells [Breast_iLN]
| PRJNA634547 | ENA
Project description:In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, by using lung tissues from humans and humanized mice, the role of human CD1c(+) and CD141(+) DCs in determining the type of CD8(+) T cell immunity generated to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8(+) T cells in vitro. However, lung-tissue-resident CD1c(+) DCs, but not CD141(+) DCs, were able to drive CD103 expression on CD8(+) T cells and promoted CD8(+) T cell accumulation in lung epithelia in vitro and in vivo. CD1c(+) DCs induction of CD103 expression was dependent on membrane-bound cytokine TGF-?1. Thus, CD1c(+) and CD141(+) DCs generate CD8(+) T cells with different properties, and CD1c(+) DCs specialize in the regulation of mucosal CD8(+) T cells.
| S-EPMC3639491 | biostudies-literature
Project description:Activation of naïve cluster of differentiation (CD)8(+) cytotoxic T lymphocytes (CTLs) is a tightly regulated process, and specific dendritic cell (DC) subsets are typically required to activate naive CTLs. Potential pathways for antigen presentation leading to CD8(+) T-cell priming include direct presentation, cross-presentation, and cross-dressing. To distinguish between these pathways, we designed single-chain trimer (SCT) peptide-MHC class I complexes that can be recognized as intact molecules but cannot deliver antigen to MHC through conventional antigen processing. We demonstrate that cross-dressing is a robust pathway of antigen presentation following vaccination, capable of efficiently activating both naïve and memory CD8(+) T cells and requires CD8?(+)/CD103(+) DCs. Significantly, immune responses induced exclusively by cross-dressing were as strong as those induced exclusively through cross-presentation. Thus, cross-dressing is an important pathway of antigen presentation, with important implications for the study of CD8(+) T-cell responses to viral infection, tumors, and vaccines.
| S-EPMC3411977 | biostudies-literature
Project description:Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8alpha+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3(-/-) mice also lack CD103+CD11b- DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3(-/-) mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b- DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3(-/-) mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8alpha+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ-resident CD8alpha+ cDCs and nonlymphoid CD103+ DCs.
| S-EPMC2856032 | biostudies-literature
Project description:In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-?1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells. Total RNA were isolated from purified human CD1c+ (BDCA1+) and CD141+ (BDCA3+) mDCs sorted from different tissues, including human blood, spleen and lungs of humanized mice, and human lungs. Eighteen samples in total were analyzed from different donors and tissues.
2013-04-04 | E-GEOD-43184 | biostudies-arrayexpress
Project description:The liver maintains a tolerogenic environment to avoid unwarranted activation of its resident immune cells upon continuous exposure to food and bacterially derived Ags. However, in response to hepatotropic viral infection, the liver's ability to switch from a hyporesponsive to a proinflammatory environment is mediated by select sentinels within the parenchyma. To determine the contribution of hepatic dendritic cells (DCs) in the activation of naive CD8(+) T cells, we first characterized resident DC subsets in the murine liver. Liver DCs exhibit unique properties, including the expression of CD8α (traditionally lymphoid tissue specific), CD11b, and CD103 markers. In both the steady-state and following viral infection, liver CD103(+) DCs express high levels of MHC class II, CD80, and CD86 and contribute to the high number of activated CD8(+) T cells. Importantly, viral infection in the Batf3(-/-) mouse, which lacks CD8α(+) and CD103(+) DCs in the liver, results in a 3-fold reduction in the proliferative response of Ag-specific CD8(+) T cells. Limiting DC migration out of the liver does not significantly alter CD8(+) T cell responsiveness, indicating that CD103(+) DCs initiate the induction of CD8(+) T cell responses in situ. Collectively, these data suggest that liver-resident CD103(+) DCs are highly immunogenic in response to hepatotropic viral infection and serve as a major APC to support the local CD8(+) T cell response. It also implies that CD103(+) DCs present a promising cellular target for vaccination strategies to resolve chronic liver infections.
| S-EPMC4369411 | biostudies-literature
Project description:In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-β1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells.
2013-04-04 | GSE43184 | GEO